215 research outputs found

    Electron Temperature and Density Fluctuations in the Daytime Ionosphere

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    Daytime incoherent scatter measurements of electron temperature and density fluctuations in F layer of ionospher

    Fundamentals of Advanced Accounting: Seventh Edition

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    Fundamentals of Advanced Accounting, 7th edition, is ideal for those schools wanting to cover twelve chapters in their advanced accounting course. This concise text allows students to think critically about accounting, just as they will do preparing for the CPA exam. The text continues to show the development of financial reporting as a product of intense and considered debate that continues today and will into the future.https://scholarship.richmond.edu/bookshelf/1319/thumbnail.jp

    Probing the role of the cation–π interaction in the binding sites of GPCRs using unnatural amino acids

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    We describe a general application of the nonsense suppression methodology for unnatural amino acid incorporation to probe drug–receptor interactions in functional G protein-coupled receptors (GPCRs), evaluating the binding sites of both the M2 muscarinic acetylcholine receptor and the D2 dopamine receptor. Receptors were expressed in Xenopus oocytes, and activation of a G protein-coupled, inward-rectifying K^+ channel (GIRK) provided, after optimization of conditions, a quantitative readout of receptor function. A number of aromatic amino acids thought to be near the agonist-binding site were evaluated. Incorporation of a series of fluorinated tryptophan derivatives at W6.48 of the D2 receptor establishes a cation–π interaction between the agonist dopamine and W6.48, suggesting a reorientation of W6.48 on agonist binding, consistent with proposed “rotamer switch” models. Interestingly, no comparable cation–π interaction was found at the aligning residue in the M2 receptor

    PIP2-Binding Site in Kir Channels: Definition by Multiscale Biomolecular Simulations†

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    Phosphatidylinositol bisphosphate (PIP(2)) is an activator of mammalian inwardly rectifying potassium (Kir) channels. Multiscale simulations, via a sequential combination of coarse-grained and atomistic molecular dynamics, enabled exploration of the interactions of PIP(2) molecules within the inner leaflet of a lipid bilayer membrane with possible binding sites on Kir channels. Three Kir channel structures were investigated: X-ray structures of KirBac1.1 and of a Kir3.1-KirBac1.3 chimera and a homology model of Kir6.2. Coarse-grained simulations of the Kir channels in PIP(2)-containing lipid bilayers identified the PIP(2)-binding site on each channel. These models of the PIP(2)-channel complexes were refined by conversion to an atomistic representation followed by molecular dynamics simulation in a lipid bilayer. All three channels were revealed to contain a conserved binding site at the N-terminal end of the slide (M0) helix, at the interface between adjacent subunits of the channel. This binding site agrees with mutagenesis data and is in the proximity of the site occupied by a detergent molecule in the Kir chimera channel crystal. Polar contacts in the coarse-grained simulations corresponded to long-lived electrostatic and H-bonding interactions between the channel and PIP(2) in the atomistic simulations, enabling identification of key side chains

    G-protein signaling: back to the future

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    Heterotrimeric G-proteins are intracellular partners of G-protein-coupled receptors (GPCRs). GPCRs act on inactive Gα·GDP/Gβγ heterotrimers to promote GDP release and GTP binding, resulting in liberation of Gα from Gβγ. Gα·GTP and Gβγ target effectors including adenylyl cyclases, phospholipases and ion channels. Signaling is terminated by intrinsic GTPase activity of Gα and heterotrimer reformation — a cycle accelerated by ‘regulators of G-protein signaling’ (RGS proteins). Recent studies have identified several unconventional G-protein signaling pathways that diverge from this standard model. Whereas phospholipase C (PLC) β is activated by Gαq and Gβγ, novel PLC isoforms are regulated by both heterotrimeric and Ras-superfamily G-proteins. An Arabidopsis protein has been discovered containing both GPCR and RGS domains within the same protein. Most surprisingly, a receptor-independent Gα nucleotide cycle that regulates cell division has been delineated in both Caenorhabditis elegans and Drosophila melanogaster. Here, we revisit classical heterotrimeric G-protein signaling and explore these new, non-canonical G-protein signaling pathways

    Ionospheric gas dynamics of satellites and diagnostic probes

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    The gas dynamics of interactions of a tenuous ionosphere with moving satellites and probes that have bearings on the diagnostics of the ionosphere are discussed. Emphasis is on the cases where the body is moving at mesothermal speeds, namely intermediate between the thermal speeds of ions and electrons of the ambient ionosphere. Methods of collision-free plasma kinetics with self-consistent field are used. The development of the topics for discussion starts with stationary Langmuir probe which entails the basic mechanism of body-plasma interaction that becomes further intricated as the body moves at a higher and higher speed. Applications of the theory of plasma interaction to meteors which move in the ionosphere are also presented.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/43801/1/11214_2004_Article_BF00212707.pd
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